CN106552284A - A kind of development embolism materials and preparation method thereof - Google Patents
A kind of development embolism materials and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a kind of development embolism materials and preparation method thereof.The barium alginate embolism microball for containing fabricated in situ barium sulfate particle that can develop is prepared using one step of electrostatic Spraying technique, realizes that developer is integrated with embolism materials, solve the problems such as indirect development and check difficulty for existing during PCI Clinical practice.Regulation and control electrostatic spray parameter, can obtain the mono-dispersion microballoon that particle diameter is 100～1000 μm, with the blood vessel embolism purposes suitable for different bores.Contrast preparation barium sulfate is simultaneously formed with barium alginate microballoon, and barium sulfate particle is evenly distributed in microballoon and fixation.Extracorporeal simulating experiment proves that the development microballoon is highly stable in 50 day testing time.Big ear rabbit right renal artery embolism experiment proves that the development microballoon of the present invention has good development effect and effect of embolization.As electrostatic Spraying technique has the characteristic of simple and fast low cost so that an one step preparation method has the potentiality of productionization.
Description
Technical field
The present invention relates to the preparation method of the embolism microball that can develop, is specially prepared and can be imaged with one step of electrostatic Spraying technique
The barium alginate embolism microball for containing fabricated in situ barium sulfate particle.
Background technology
Evaluation for interventional therapy through uterine artery is whole to be carried out under the guiding and monitoring of image documentation equipment, the conduit, pin by insertion internal organs
Embolism materials are injected the Ink vessel transfusing of diseased organ on apparatus, middle clinopodium polycephalum blocks the nutrition supply to diseased region, suppress swollen
Knurl grows.Which has the advantages that accurately to go directly, and focus, wound are little, risk is low, recovery is fast, and the embolism for being widely used to tumour is controlled
Treat.
But there is problems with Clinical practice in the technology：
(1) shortage of autography embolism materials.In order to, in interventional procedure, monitor embolism materials importing in vivo
With embolism situation, the contrast preparation of one class of heavy metallic salt, small molecule containing iodine, Huan Zhechang during intervention operation, need to be added in embolism materials
Therefore various bad reactions such as oedema, Nausea and vomiting are produced.Contrast preparation is separated with embolism materials so that seen under image documentation equipment
The developing result for measuring can not reflect the truth of embolism materials comprehensively, deviation occur.In addition, excessive free contrast preparation
Toxic and side effect can be produced to body also.
(2) check difficult.In order to position and track embolism materials, to judge the effect of PCI, postoperative check every time
Again radiography is needed all.Repeatedly puncture insertion conduit to inject contrast preparation, not only increased medical expense, also considerably increase sufferer
Pain.
(3) homogeneity and controllability of embolism materials size.Embolism agent of granule is a kind of embolism materials for using earliest, but
Commercially available granular pattern suppository particle size distribution range is all relatively wide.During embolism, too small embolism agent of granule is easily from lesions position
Vessel leakage, is retained by lung into blood circulation, causes dystopy embolism；And excessive particle can be because reaching distal end
Minute blood vessel cause effect of embolization incomplete.Further, since the bore difference of different blood vessel is very big, same embolism agent of granule
Can different particle diameters be made according to the size at embolism position be also a problem.
Therefore need one kind badly to develop embolism microball, Microsphere Size so that development effect can be controlled according to client need
It is controllable.
The content of the invention
Based on above the deficiencies in the prior art, technical problem solved by the invention is to provide one kind application high-pressure electrostatic
By Polymer Solution be prepared into particle diameter from nanometer to micron, the other particle of grade develop the preparation method of embolism materials, should
The preparation method short preparation period of development embolism materials, easy to operate, process are gentle, equipment cost is relatively low, and obtained load
The size tunable of medicine particle, distribution are narrower, with reasonable self-dispersing.Electrostatic spray is for the limit for preparing material simultaneously
Make less, the especially application of coaxial electrostatic spray technique so that various oil-solubles and water soluble drug are all easier to be downloaded to
In particle, the potential quality for carrying medicine particle universal method is prepared with becoming.
In order to solve above-mentioned technical problem, the present invention provides a kind of preparation method of development embolism materials, including following step
Suddenly：
Fig. 1 is the preparation facilities and preparation process schematic diagram of preferred embodiment of the present invention development embolism materials.The present invention is aobvious
The preparation method of shadow embolism materials, comprises the steps：
Step one：The preparation of solution.By sodium alginate and sodium sulphate co-dissolve in deionized water, being prepared into concentration is
The sodium alginate and 0～0.5mol/L sodium sulphate mixed solution of 1%～3% (w/v) is used as EFI liquid；Barium chloride is dissolved in deionization
In water, it is collection liquid to be prepared into the barium chloride solution that concentration is 0.1～0.8mol/L；
Step 2：The preparation of development microballoon.EFI liquid obtained in step one is sprayed in collection liquid using sprayer unit, spray
Collection liquid is slowly stirred during mist, the mixed liquor of the barium alginate microballoon rich in load barium sulfate particle is obtained；Preferably, spray
Mist device is electrostatic spray devices.
EFI liquid is placed in into the sampling device of electrostatic spray devices, it is 0.1～10mL/hr to adjust sample introduction speed.To fill
The collection ware of collection liquid is placed in immediately below shower nozzle at 4～20cm, and is slowly stirred collection liquid, it is to avoid not completely crued microballoon glues
Connect together.Annular electric circle is placed in below shower nozzle at 2cm, for the spray regime of restricting liquid drop.The internal diameter of shower nozzle be 0.1～
3mm.Shower nozzle connects a DC high-voltage power supply, and regulation voltage is 3～30kv.Annular electric circle connects another high voltage power supply, adjusts
Voltage is 0～10kv.Collect ware ground wire.
DC high-voltage power supply is opened, between shower nozzle and collection ware, high voltage electric field is produced.Meanwhile, produce in EFI liquid a large amount of of the same race
Electric charge, mutually exclusive generation electrostatic repulsion between electric charge.If electrostatic repulsion exceedes the surface tension of solution, sodium alginate and sulphur
The mixed solution of sour sodium will be split into the micron order drop of uniform particle diameter by electrostatic force.Subsequently, drop is in the presence of electric field force
Directive collects ware.When drop contact collection liquid is mixed, the barium ions of collection liquid middle and high concentration is rapidly diffused in mixed solution,
There is ion-exchange reactions with the sodium ion in sodium alginate in a part of barium ions, make sodium alginate drop be cross-linked to form solid-state sea
Barium alginate microballoon；Meanwhile, another part barium ions is reacted with the sulfate ion of sodium sulphate in mixed liquor, is formed in situ barium sulfate
The particle barium alginate microballoon tight that is being crosslinked is in its cross-linked network.Because the contrast preparation and barium alginate
What microballoon was simultaneously formed, barium sulfate particle is evenly distributed in microballoon and fixation.Thus obtain loading barium sulfate particle
Barium alginate microballoon.
Step 3：The collection of development microballoon, will be the obtained barium alginate rich in load barium sulfate particle in step 2 micro-
The mixed liquor of ball, standing 1～3hr makes the abundant gelation of barium alginate；Centrifugation 2000～4000rpm collect microballoon, and spend from
Sub- water washing 3～10 times both development embolism materials of the present invention
Preferably, step 3 is：The collection of development microballoon.By the obtained sea rich in load barium sulfate particle in step 2
The mixed liquor of Barium alginate microballoon, standing 2hr makes the abundant gelation of barium alginate；Centrifugation 3000rpm collects microballoon, and uses deionization
Water washing 5 times, both development embolism materials of the present invention.Development embolism materials are vacuum dried or are dispersed in deionized water
In -4 DEG C preservation
A kind of development embolism materials, are that sodium alginate and 0～0.5mol/L sodium sulphate that concentration is 1%～3% (w/v) are mixed
Close the EFI liquid of solution to spray into during concentration is the collection liquid of barium chloride solution of 0.1～0.8mol/L through electrostatic atomizer,
Standing 2hr makes the abundant gelation of barium alginate；Centrifugation 3000rpm collects microballoon, and is washed with deionized 5 gained.This shows
Shadow embolism materials are vacuum dried or disperse -4 DEG C of preservations in deionized water.
Compared with prior art, technical scheme has the advantages that：
Electrostatic Spraying technique is that Polymer Solution is prepared into particle diameter from nanometer to micron even using high-voltage electrostatic field
The technology of the other particle of grade.Its short preparation period, easy to operate, process are gentle, equipment cost is relatively low, and obtained load
The size tunable of medicine particle, distribution are narrower, with reasonable self-dispersing.Electrostatic spray is for the limit for preparing material simultaneously
Make less, the especially application of coaxial electrostatic spray technique so that various oil-solubles and water soluble drug are all easier to be downloaded to
In particle, the potential quality for carrying medicine particle universal method is prepared with becoming.
The present invention prepares the alginic acid for containing fabricated in situ barium sulfate particle that can develop using one step of electrostatic Spraying technique
Barium embolization microballoon, realizes that developer is integrated with embolism materials, solves exist during PCI Clinical practice indirect
The problems such as development and difficult check.As electrostatic Spraying technique has the characteristic of simple and fast low cost so that prepared by a step
Method has the potentiality of productionization.By the simple tune to electrostatic spray parameter (such as jet size, voltage, EFI liquid concentration etc.)
Control, obtains the mono-dispersion microballoon that particle diameter is 100～1000 μm, to be adapted to the blood vessel embolism purposes of difference bore.By to marine alga
The regulation and control of the ratio and corresponding barium chloride concentration of sour sodium and sodium sulphate, can control the radiopacit of embolism microball.Cause
It is simultaneously formed for the contrast preparation barium sulfate and barium alginate microballoon, barium sulfate particle is evenly distributed in microballoon and fix tightly
Gu.Extracorporeal simulating experiment proves that the development microballoon is highly stable, and Jing detects that the size and development effect of microballoon be not larger for 50 days
Change.Big ear rabbit right renal artery embolism experiment proves that the development microballoon of the present invention has good development effect and effect of embolization.
Sodium alginate is a kind of embolism materials for being widely used in clinic in itself, with good biocompatibility.The present invention is in its base
Introduce the good heavy metallic salt of security to realize CT developments, the potentiality with clinical practice on plinth.Additionally, due to coaxial electrostatic
The characteristic of spray technique, various oil-solubles and water soluble drug are all easier to be downloaded in particle so that the present invention is carried to prepare
Medicine particle universal method provides a kind of new approach.
Described above is only the general introduction of technical solution of the present invention, in order to better understand the technological means of the present invention,
Can be practiced according to the content of specification, and in order to allow the present invention above and other objects, features and advantages can be more
Become apparent, illustrate below in conjunction with preferred embodiment, describe in detail as follows.
Description of the drawings
In order to be illustrated more clearly that the technical scheme of the embodiment of the present invention, below the accompanying drawing to embodiment is simply situated between
Continue.
Fig. 1：The schematic diagram of electrostatic spray devices and embolism microball preparation process of can developing.Wherein NaAlg represents alginic acid
Sodium, Na2SO4Represent sodium sulphate, BaCl2Barium chloride is represented, BaAlg represents barium alginate, BaSO4@BaAlg represent load sulfuric acid
The barium alginate microballoon of barium；
Fig. 2：The pattern of the barium alginate microballoon of load barium sulfate.Wherein, optical microscope photographs of the A for microballoon, B are micro-
The stereoscan photograph of ball surface, stereoscan photographs of the C for microballoon cross section；
Fig. 3：The X ray diffracting spectrum (XRD) of the barium alginate embolism microball of load barium sulfate.Wherein vertically black line is
The standard X-ray diffraction collection of illustrative plates (No.24-1035) of barium sulfate in JCPDs databases；
Fig. 4：The particle diameter of the barium alginate microballoon of load barium sulfate and the relation of electrostatic spray jet size.
Fig. 5：The optical microscope photograph of the barium alginate microballoon of load barium sulfate.Wherein, A～E is represented in shower nozzle respectively
The optical microscope photograph of the development microballoon that footpath is prepared when being 0.18,0.26,0.41,0.84 and 1.19mm, scale are 500 μ
m；
Fig. 6：The particle diameter of the barium alginate microballoon of load barium sulfate and the relation of electrostatic spray voltage.
Fig. 7：The optical microscope photograph of the barium alginate microballoon of load barium sulfate.Wherein, A～D represent voltage respectively as
The optical microscope photograph of the development microballoon prepared when 14kv, 10kv, 5kv and 3kv, scale are 500 μm；
Fig. 8：The particle diameter of the barium alginate microballoon of load barium sulfate and the relation of electrostatic spray sample introduction speed.
Fig. 9：The optical microscope photograph of the barium alginate microballoon of load barium sulfate.Wherein, A～D is respectively sample introduction speed
For 0.3,0.6,1 and 2mL/hr when, the optical microscope photograph of microballoon, scale are 500 μm；
Figure 10：The optical microscope photograph of the barium alginate microballoon of load barium sulfate.Wherein, A is calcium alginate (CaAlg)
Microballoon, when B～F is that sodium sulfate concentration is respectively 0,0.05,0.1,0.2 and 0.3mol/L in EFI liquid, preparation contains sulfuric acid
Barium alginate microballoon BaAlg, BaAlg-0.05M, BaAlg-0.1M, BaAlg-0.2M and BaAlg-0.3M of barium, scale are
200μm；
Figure 11：The radiopacit of the barium alginate microballoon of load barium sulfate.Wherein, Upper panel be respectively CaAlg,
Photo of BaAlg, BaAlg-0.05M, BaAlg-0.1M, BaAlg-0.2M and BaAlg-0.3M microballoon under X-ray, lower section is
Relative signal intensity of the imaging system according to the brightness calculation of corresponding microballoon photo；
Figure 12：The vitro stability test of the barium alginate microballoon of load barium sulfate.Wherein A is to develop microballoon before testing
The microphotograph of (figure b) after (figure a) and test, scale are 500 μm.B is the development microballoon that measures of small animal imaging instrument to X
The signal strength signal intensity of ray stopping power and the relation curve of testing time；
Figure 13：(figure A), the 2nd week (figure B) and the 3rd the 1st week after the development microballoon embolism of the big ear rabbit right renal artery present invention
The CT scan figure in week (figure C), in figure, the position of circles mark is right kidney；
Figure 14：Big ear rabbit right renal artery the 1st week after development microballoon embolism (figure A) and the DR images of the 3rd week (figure B),
In figure, the position of circles mark is right kidney；
Figure 15：Big ear rabbit right renal artery with development microballoon embolism 3 weeks after death, the photo of left kidney and right kidney.The left side is
Left kidney, the right for right kidney.
Specific embodiment
The following detailed description of the present invention specific embodiment, its part as this specification, by embodiment come
Illustrate the principle of the present invention.Other aspects of the present invention, feature and its advantage will be become apparent by the detailed description.
Embodiment 1：The preparation of the barium alginate microballoon of load barium sulfate
The sample introduction dress of electrostatic spray devices is put into as EFI liquid with 2% (w/v) sodium alginate and 0.3mol/L sodium sulphate
Put, it is 0.3mL/hr to adjust sample introduction speed.With the barium chloride solution of 0.6mol/L as collection liquid, 9cm immediately below shower nozzle is placed in
Place, and it is slowly stirred collection liquid.Annular electric circle is placed in below shower nozzle at 2cm, for the spray regime of restricting liquid drop.Shower nozzle it is interior
Footpath is 0.18mm.Shower nozzle connects a DC high-voltage power supply, and regulation voltage is 10kv.Annular electric circle connects another high voltage power supply,
Regulation voltage is 2kv.Collect ware ground wire.DC high-voltage power supply is opened, EFI liquid is split into the micro- of uniform particle diameter by electrostatic force
Meter level drop, is subsequently reacted with collection liquid, and a step forms the barium alginate microballoon of load barium sulfate particle.Electrostatic spray devices and
Preparation process schematic diagram is as shown in Figure 1.After the completion of reaction, standing 2hr makes the abundant gelation of barium alginate.Centrifugation 3000rpm is received
Collection microballoon, and it is washed with deionized 5 times.Vacuum drying or dispersion -4 DEG C of preservations in deionized water.
The microballoon being dispersed in water with optical microscope inspection, as shown in Figure 2 A, it is found that the method balling-up is good, and microballoon is big
Little homogeneous, average grain diameter is 160 μm of (n>300).By scanning electron microscope observation, the surface compact of microballoon is smooth without barium sulfate particle
(Fig. 2 B), and barium sulfate particle is evenly distributed on the cross section of microballoon, and by tight in barium alginate carrier (Fig. 2 C).
Fig. 3 shows the X ray diffracting spectrum of the barium alginate embolism microball of load barium sulfate and the standard of barium sulfate in JCPDs databases
X ray diffracting spectrum (No.24-1035) is consistent, and each crystal face can be corresponded, it was demonstrated that the presence of barium sulfate in embolism microball.
Embodiment 2：The control of development microspherulite diameter
Preparation method is consistent with embodiment 1.The present embodiment is only used for enumerating partial example, shows by joining to electrostatic spray
Several simple regulation and control, you can obtain the mono-dispersion microballoon of different-grain diameter, are applicable to the blood vessel embolism purposes of different bores.
When keeping, the other specification of electrostatic spray is constant, and when only increasing shower nozzle internal diameter, the particle diameter of embolism microball increases therewith.
As shown in figure 4, when shower nozzle internal diameter increases to 1.19mm from 0.18mm, 0.26mm, 0.41mm, 0.84mm, the particle diameter of microballoon with
Increase to 490 ± 23 μm from 160 ± 7 μm, 220 ± 18 μm, 320 ± 17 μm, 410 ± 27 μm.The pattern of gained development microballoon
As shown in figure 5,5A～5E represent shower nozzle internal diameter respectively as 0.18,0.26,0.41,0.84 and 1.19mm when the development microballoon for preparing
Optical microscope photograph.
When keeping, the other specification of electrostatic spray is constant, when shower nozzle internal diameter is 0.26mm, reduces spray voltage, embolism microball
Particle diameter increase therewith.As shown in fig. 6, when voltage is reduced to 3kv from 14kv, 10kv, 5kv, the particle diameter of microballoon is from 190 ± 12
μm, 220 ± 18 μm, 500 ± 25 μm increase to 910 ± 21 μm.The pattern of gained development microballoon is as shown in fig. 7,7A～7D difference
Represent voltage as 14kv, 10kv, 5kv and 3kv when prepare development microballoon optical microscope photograph.
Embodiment 3：The extension of development method for preparing microsphere
Preparation method is consistent with embodiment 1.The present embodiment is only used for enumerating partial example, it was demonstrated that the preparation method of the present invention
Being easily enlarged.
As shown in figure 8, when keep electrostatic spray other specification it is constant, sample introduction speed from 0.3mL/hr, 0.6mL/hr,
When 1mL/hr increases to 2mL/hr, the particle diameter of thus obtained microsphere be respectively 160 ± 7 μm, 164 ± 9 μm, 170 ± 11 μm, and 168 ± 9
μm.Gained development microballoon pattern as shown in figure 9,9A～9D respectively for sample introduction speed be 0.3,0.6,1 and 2mL/hr when prepare
Development microballoon optical microscope photograph.The particle diameter and monodispersity of microballoon is not all changed much.I.e. when output increased about
When 10 times, the quality of the microballoon that develops is still in tolerance interval.Illustrate that the preparation method of the present invention can be magnified.In addition, by
There is the characteristic of simple and fast low cost in electrostatic Spraying technique so that an one step preparation method of the present invention has the latent of productionization
Power.
Embodiment 4：The control of development microballoon radiopacit
Preparation method is consistent with embodiment 1.The present embodiment is only used for enumerating partial example, shows by joining to electrostatic spray
Several simple regulation and control, you can obtain development microballoon impervious with different x-ray, go for different demands.
With sodium alginate as EFI liquid, when calcium chloride is as collection liquid, calcium alginate (CaAlg) microballoon can be obtained.
With the sodium sulphate of sodium alginate and variable concentrations as EFI liquid, when barium chloride is as collection liquid, can prepare and penetrate with different X
The impervious development microballoon of line.When the concentration of sodium sulphate is respectively 0,0.05,0.1,0.2 and 0.3mol/L, gained is contained
The barium alginate microballoon of barium sulfate is respectively labeled as BaAlg, BaAlg-0.05M, BaAlg-0.1M, BaAlg-0.2M and BaAlg-
0.3M.As shown in Figure 10,10A～10D distinguishes CaAlg, BaAlg, BaAlg-0.05M, BaAlg- to the pattern of gained development microballoon
The optical microscope photograph of 0.1M, BaAlg-0.2M and BaAlg-0.3M microballoon.Their appearance and size is basically identical, is
220μm。
The microballoon of same volume is put in 24 orifice plates, with the x-ray imaging system (IVISLumina of small animal imaging instrument
XR system) come detect development microballoon radiopacit.Above Figure 11 be respectively CaAlg, BaAlg, BaAlg-0.05M,
Photo of BaAlg-0.1M, BaAlg-0.2M and BaAlg-0.3M microballoon under X-ray, lower section are imaging system according to corresponding micro-
The relative signal intensity of the brightness calculation of ball photo.The X-ray of calcium alginate (CaAlg) microballoon blocks that ability is worst, and microballoon is most
Secretly, signal strength signal intensity is 2800.When the concentration of sodium sulphate in EFI liquid increases to 0.3mol/L from 0,0.05,0.1,0.2, contain
The radiopacit of the barium alginate microballoon of barium sulfate strengthens, and microballoon gradually brightens, signal strength signal intensity is respectively 3343,4220,
4988th, 6008 and 6440.
Embodiment 5：The vitro stability test of development microballoon
The barium alginate microballoon that 0.5g contains barium sulfate is put in 10mL centrifuge tubes, add 5mL PBS, be placed in 37 DEG C it is permanent
Shake in temperature vibration case, rotating speed is 200rpm.2mL PBS are taken out daily and supplement the fresh PBS of 2mL.Set time take out from
Heart pipe, detects the X-ray of development microballoon with the x-ray imaging system (IVISLumina XR system) of small animal imaging instrument
Impermeability.
Figure 12 A be microballoon before testing (Figure 12 A (a)) and test after (Figure 12 A (b)) microphotograph, 12B is petty action
Development signal strength signal intensity of the microballoon to X-ray blocking capability and the relation curve of testing time that thing imager is measured.Such as Figure 12 institutes
Show, Jing detects that the size of microballoon is changed into 183 ± 6 μm from 164 ± 9 μm, and microballoon balling-up improves in 53 days；While device signal
Intensity declines 2.5%.After illustrating constant temperature oscillation 53 days, development microballoon has slight water suction phenomenon, expands, grain after development microballoon water suction
Footpath becomes big, and microballoon is rounded.And as microsphere volume expansion causes barium sulfate particle density to reduce, therefore under radiopacity
Drop, signal strength weakening.Prove that development microballoon prepared by the present invention has high stability, can keep good in embolotherapy
Good effect of embolization and development effect.
Embodiment 6：The application of development microballoon
Preparation method is consistent with embodiment 1.The present embodiment is only with the development microballoon embolism large ear rabbit that particle diameter is 320 μm
Right kidney, for obvious shadow microballoon certain applications.
Japan large ear rabbit is taken, front 12 hours fasting, water is tested.After rabbit anesthesia, dorsal position is fixed, right side groin preserved skin
And sterilize, skin of groin to be cut, and is exposed right common femoral artery and exposed femoral artery is separated with haemostatic clamp, two ends put silk thread,
Lift two ends silk thread, femoral artery is separated with peripheral muscle tissue.Then it is direct with Jing puncture needles after lancet puncture femoral artery
Coaxial microtubular is inserted, microtubular is placed in into abdominal aorta.Hand push contrast agent, specifies microtubular after right renal artery opening
Trans-abdominal sustainer selects intubation to right renal artery, bolus administration of contrast agent Iohexol, makes right renal artery radiography, Jing microtubulars develop micro-
Ball injects right renal artery, makes distal aorta embolism.Operation end ligatures point of puncture distal end femoral artery after removing pipe, continue to raise after suture
Support.
After development microballoon embolism, the big ear rabbit state of mind is normal with diet, has no adverse reaction.After embolism, with CT and DR
To check, the embolism situation of microballoon is detected.Figure 13 is the 1st week (Figure 13 A), the 2nd week (Figure 13 B) after big ear rabbit right renal artery embolism
With the CT scan figure of the 3rd week (Figure 13 C), in figure, the position of circles mark is right kidney.It is white bright in CT scan figure circle position
Point is the embolism microball in right kidney, and the microballoon that develops in three time-of-weeks is high-visible, and its brightness and density not with
There is significant change in the time, it was demonstrated that the development microballoon embolism of the present invention firmly, does not occur dystopy.Equally, DR figures can also be helped
Demonstrate,prove this conclusion.Figure 14 is the DR images of the 1st week (Figure 14 A) and the 3rd week (Figure 13 B) after big ear rabbit right renal artery embolism, is schemed
The position of middle circles mark is right kidney.In circle position, black casting shape part is the right renal artery blood of developed microballoon embolism
Pipe, the not no phenomenon in the corresponding position of the left kidney of picture, it was demonstrated that the development microballoon of present invention development capability under X-ray is good.
In three time-of-weeks after embolism, the right renal artery blood vessel of developed microballoon embolism is high-visible, and its definition without with
There is significant change in the time.Prove that the development microballoon development effect of the present invention is good, the developer barium sulfate particle that original position contains
With embolism microball barium alginate microballoon without segregation phenomenon；The embolism ability of development microballoon is good, embolism firmly without dystopy phenomenon, especially
Which is that the effect of embolization to distal aorta is good.
After big ear rabbit right renal artery development microballoon embolism 3 weeks checking is finished, put to death, taken out its left and right kidney,
Observe its color and surface condition.Figure 15 is the photo of left kidney and right kidney, wherein, the left side for left kidney, the right for right kidney.Can
It is smooth flexible with the scarlet surface of left kidney color for finding non-embolism；And the right nephrarctia of embolism is turned white, surface relief is uneven, extensively
General fibrillatable, is coagulation necrosis performance.It is possible thereby to prove that the development microballoon effect of embolization of the present invention is good.
The present invention prepares the alginic acid for containing fabricated in situ barium sulfate particle that can develop using one step of electrostatic Spraying technique
Barium embolization microballoon, realizes that developer is integrated with embolism materials, solves exist during PCI Clinical practice indirect
The problems such as development and difficult check.As electrostatic Spraying technique has the characteristic of simple and fast low cost so that prepared by a step
Method has the potentiality of productionization.By the simple tune to electrostatic spray parameter (such as jet size, voltage, EFI liquid concentration etc.)
Control, can obtain the mono-dispersion microballoon that particle diameter is 100～1000 μm, to be adapted to the blood vessel embolism purposes of difference bore.By right
The regulation and control of the ratio and corresponding barium chloride concentration of sodium alginate and sodium sulphate, the X-ray that can control embolism microball are impermeable
Property.Because what the contrast preparation barium sulfate and barium alginate microballoon were simultaneously formed, barium sulfate particle be evenly distributed in microballoon and
Fixation.Extracorporeal simulating experiment proves that the development microballoon is highly stable, and Jing detects that the size and development effect of microballoon do not have in 50 days
There is large change.Big ear rabbit right renal artery embolism experiment proves that the development microballoon of the present invention has good development effect and embolism
Effect.Sodium alginate is a kind of embolism materials for being widely used in clinic in itself, with good biocompatibility.The present invention exists
Introduce the good heavy metallic salt of security to realize CT developments, the potentiality with clinical practice on the basis of which.Additionally, due to coaxial
The characteristic of electrostatic Spraying technique, various oil-solubles and water soluble drug are all easier to be downloaded in particle so that the present invention is system
The standby medicine particle universal method that carries provides a kind of new approach.
The above is the preferred embodiment of the present invention, and the right model of the present invention can not be limited certainly with this
Enclose, it is noted that for those skilled in the art, under the premise without departing from the principles of the invention, may be used also
To make some improvement and variation, these improve and variation is also considered as protection scope of the present invention.
Claims (10)
1. it is a kind of development embolism materials preparation method, it is characterised in that comprise the steps：
Step one：The preparation of solution, by sodium alginate and sodium sulphate co-dissolve in deionized water, is prepared into concentration for 1%
The sodium alginate and 0～0.5mol/L sodium sulphate mixed solution of～3% (w/v) is used as EFI liquid；Barium chloride is dissolved in deionized water
In, it is collection liquid to be prepared into the barium chloride solution that concentration is 0.1～0.8mol/L；
Step 2：The preparation of development microballoon, EFI liquid obtained in step one is sprayed in collection liquid using sprayer unit, was sprayed
Collection liquid is slowly stirred in journey, the mixed liquor of the barium alginate microballoon rich in load barium sulfate particle is obtained；
Step 3：The collection of development microballoon, by the obtained barium alginate microballoon rich in load barium sulfate particle in step 2
Mixed liquor, standing 1～3hr makes the abundant gelation of barium alginate；2000～4000rpm of centrifugation collects microballoon, and deionized water
Washing 3～10 times both development embolism materials of the present invention.
2. the preparation method of development embolism materials as claimed in claim 1, it is characterised in that：In the step 2, spraying dress
It is set to electrostatic spray devices.
3. the preparation method of development embolism materials as claimed in claim 1 or 2, it is characterised in that：In the step 2, spraying
The internal diameter of the shower nozzle of device be 0.1～3mm, shower nozzle connection DC high-voltage power supply, voltage be 3～30kv.
4. the preparation method of development embolism materials as claimed in claim 1 or 2, it is characterised in that：It is in the step 2, described
Annular electric circle is provided with below the shower nozzle of sprayer unit, annular electric circle connects high voltage power supply, and voltage is 0～10kv.
5. the preparation method of development embolism materials as claimed in claim 4, it is characterised in that：In the step 2, the ring
Shape electric circle is arranged at 2cm below the shower nozzle of the sprayer unit.
6. the preparation method of development embolism materials as claimed in claim 1 or 2, it is characterised in that：In the step 2, spraying
The sample introduction speed of device is 0.1～10mL/hr.
7. the preparation method of development embolism materials as claimed in claim 1 or 2, it is characterised in that：The step 3 is development
The collection of microballoon, by the mixed liquor of the obtained barium alginate microballoon rich in load barium sulfate particle in step 2, standing 2hr makes
The abundant gelation of barium alginate；Centrifugation 3000rpm collect microballoon, and be washed with deionized 5 times both it is of the present invention show
Shadow embolism materials.
8. the preparation method of development embolism materials as claimed in claim 1 or 2, it is characterised in that：The development embolism materials
Vacuum drying or dispersion -4 DEG C of preservations in deionized water.
9. a kind of development embolism materials, it is characterised in that：Development embolism materials are the sodium alginate that concentration is 1%～3% (w/v)
Chlorination that concentration be 0.1～0.8mol/L is sprayed into through sprayer unit with the EFI liquid of 0～0.5mol/L sodium sulphate mixed solutions
In the collection liquid of barium solution, standing 2hr makes the abundant gelation of barium alginate；Centrifugation 3000rpm collects microballoon, and deionized water
5 gained of washing.
10. develop embolism materials as claimed in claim 9, it is characterised in that：It is described development embolism materials vacuum drying or
Dispersion -4 DEG C of preservations in deionized water.
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| CN113967269A (en) * | 2020-07-23 | 2022-01-25 | 华中科技大学 | Medicine-carrying polyvinyl alcohol embolism microsphere with magnetic resonance development effect and preparation method thereof |
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| CN108114308A (en) * | 2017-12-28 | 2018-06-05 | 苏州恒瑞迦俐生生物医药科技有限公司 | Autography embolism microball with high density element and preparation method thereof |
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| CN113967269A (en) * | 2020-07-23 | 2022-01-25 | 华中科技大学 | Medicine-carrying polyvinyl alcohol embolism microsphere with magnetic resonance development effect and preparation method thereof |
| CN113967269B (en) * | 2020-07-23 | 2023-02-21 | 华中科技大学 | Medicine-carrying polyvinyl alcohol embolism microsphere with magnetic resonance development effect and preparation method thereof |
| CN111773428A (en) * | 2020-08-05 | 2020-10-16 | 华中科技大学 | Medicine sustained-release alginic acid embolism microsphere and preparation method thereof |
| CN117815434A (en) * | 2024-03-05 | 2024-04-05 | 山东第二医科大学 | Oxidized regenerated cellulose embolism microsphere and preparation method thereof |
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